Subhash Mukhopadhyay (physician)
Encyclopedia
Subhash Mukhopadhyay (January 16, 1931 - June 19, 1981) was a physician from Kolkata
, India
.
, which was then affiliated with the prestigious University of Calcutta
. He would later earn a doctorate from the University of Calcutta in 1958 reproductive physiology under the stewardship of Prof. Sachchidananda Banerjee. Later he would earn a second doctorate from the University of Edinburgh
in 1967 in reproductive endocrinology,
His life and death has been the subject of countless newspaper reviews and inspired the Hindi
movie Ek Doctor Ki Maut
(Death of a doctor), directed by Tapan Sinha
.
physicians Patrick Steptoe
and Robert Edwards) to perform the In vitro fertilization resulting in a test tube baby "Durga" (alias Kanupriya Agarwal) on October 3, 1978.
Facing social ostracization, bureaucratic negligence, reprimand and insult
instead of recognition
from the West Bengal government and refusal of the Government of India
to allow him to attend international conferences, he committed suicide in his Calcutta residence on 19 June 1981.
His feat has been given belated recognition as the Indian physician who in 1986 was "officially" regarded as being the first doctor to perform in-vitro fertilization in India.
His recognition is attributable to TC Anand Kumar who is credited to be the mastermind behind India's second (officially the first) test-tube baby. Kumar took the crown off his own head after reviewing Subhash Mukhopadhyay's personal notes. He was ably helped by Sunit Mukherji, who was a one-time colleague of Mukhopadhyay.
Kumar is currently active in setting up a research institute in reproductive biology
in memory of Mukhopadhyay.
Ovarian stimulation. In his report dated 19-10-1978 to the DHS, Mukherjee stated that he had treated Mrs Agarwal with hMG ampoules given twice a day and on alternate days and starting from day 3 to day 9 of the cycle. She was given 6000 I.U. of hCG on day 11 of the cycle and she was subjected to oocyte aspiration some 48h later. Mukherjee was able to aspirate 5 folicle by this method. In today's context this ovarian protocol will not sound outrageous because controlled ovarian hyperstimulation is the standard procedure for all women subjected to IVF. However, until 1980 December ‘conventional wisdom’ in Britain, Australia and USA dictated that stimulated cycles were unsuitable for oocyte collection and therefore oocyte aspiration was restricted to natural cycles. It was only in 1981 that other scientists resorted to ovarian stimulation. The Australians who were the next to announce the birth of IVF babies, began to use clomiphene citrate for ovarian stimulation in 1981. The Norfolk group in the USA, who were the third to report the occurrence of an IVF baby, began to use hMC and hCG in their IVF programme with success in 1982. It is noteworthy that Mukherjee was far ahead of his time in successfully using an ovarian stimulation protocol before anyone else in the world had thought of doing so.
Ovum pick-up for IVF was a problem during the early days. The British team had used a laparascope to harvest oocytes. The advent of ultrasonography later on opened out a new avenue to aspirate oocytes transvesically under ultrasound guidance by making a percutaneous insertion of a long needle traversing the abdominal wall, the urinary bladder and finally the ovarian follicle. The advent of the transvaginal probe has made it possible to collect oocytes per vaginam and this is the standard procedure used now.
Mukherjee ’s originality was that he was able to access the ovaries by a very simple operation on the wall of the vagina. Stimulated ovaries enlarge and drop down towards the Pouch of Douglas. A small incision on the posterior wall of the vagina would allow the ovaries to fall into this opening. This reminds one of how a biologist gains rapid access to the ovaries of rats by a very simple lateral, abdominal incision. The entire procedure was accomplished within a couple of minutes. Mukherjee ’s research experience with rats and humans had helped him take this very simple and original approach of gaining access to ovaries by posterior colpotomy.
One wonders why this very simple approach did not gain popularity. After all today oocytes are aspirated per vaginam under ultrasound guidance.
The methods of in vitro fertilization and embryo growth are described in detail in Mukherjee ’s letter to the DHS dated 19 October 1978 as well as in a publication in an obscure journal. Mukherjee ’s stated ‘…It also appears that for cryogenic preservation of embryos with a relatively larger number of blastomeres (more than 8 cells) may be preferable’.
‘Few pre-ovulatory human oocytes collected from a married woman by surgery were fertilized with spermatozoa from the husband and cleaved in vitro and subsequently frozen slowly to about 196oC after stepwise treatment with dimethyl sulfoxide. One such frozen embryo was subsequently thawed slowly and when transferred into the uterus of the woman apparently resulted in the production of a clinically normal female baby after normal period of gestation’.
Here is clear published evidence of how exactly Mukherjee carried out his version of in vitro fertilization and embryo transfer.
Cryopreservation of embryos from mice, rabbits, sheep and goats were reported between 1971 and 1979. The first report on the successful cryopreservation of four to eight cell human embryos appeared as late as 1981 and Trounson and Mohr reported the first successful clinical outcome of the transfer of thawed human embryos in 1983. A WHO report states ‘embryo cryopreservation has now become a routine adjunct to IVF procedures, and various methods of freezing are employed. The method that has yielded the best results in terms of simplicity, efficiency and reproducibility is one that involves freezing of one to three-day-old embryos (one to eight cells) in a controlled biological chamber that cools the embryos to sub-zero temperatures in the presence of a cryoprotectant 1,2 propanediol. Other cryoprotectants that are used are dimethyl sulfoxide (the same cryoprotectant was used by Mukherjee ) and glycerol.
It may be noted that Subhas Mukherjee reported the successful cryopreservation of an eight cell embryo, storing it for 53 days, thawing and replacing it into the mother’s womb, resulting in a successful and live birth as early as 1978- a full five years before anyone else had done so. This small publication of Mukherjee in 1978 clearly shows that Mukherjee was on the right line of thinking much before anyone else had demonstrated the successful outcome of a pregnancy following the transfer of a 8-cell frozen-thawed embryo into human subjects transferring 8-cell cryopreserved embryos.” (Current Science, Vol .72. No. 7, 10th april1997)
The Committee put forward its final verdict, “Everything that Dr. Mukhopadhyay claims is bogus.”
Only 67 days earlier, on 25 July 1978, world’s first human test tube baby Louise Joy Brown was born at Oldham General Hospital in England. Architects were Robert Edward and Patrick Steptoe. In their procedure they collected an ovum by using a laparoscope. At first they observed the evolution and development of the ovum for a long time and then collected it through a small incision. The ovum thus collected is then fertilized by sperm on a small disc. When it forms into an embryo scientists placed it into the womb. But Mukhopadhyay without using a laparoscope collected the ovum by performing a small operation in the vagina. He increased the number of ova collected by using hormones and developed an embryo. Lastly, he placed it in the womb.
Thanks to his peers and Government bureaucrats he was ultimately handed a punishment. He had been transferred to an ophthalmic department which sealed his prospect of working on hormones.
“The brief description given by Mukherjee in his letter dated 19 October 1978 to the Director of Health Services, Government of West Bengal, the reports he gave over the television interviews and reported in the lay press describe how Mukherjee carried out the procedure of in vitro fertilization.
In T.C. Anand Kumar’s initiative, Mukhopahdhyay was mentioned as the architect of first Indian test tube baby in a document related to the subject of artificial intercourse in ICMR. India’s first test tube baby “Durga”, whose parental name is Kanupriya Agarwal, works in a Multinational Company as a Marketing Executive in Delhi. On her 25th birthday she first exposed her identity in a ceremony organized in the memory of Mukhopahdhyay. She spoke about her creator in front of the media and proved once again that her creator’s claim was not bogus.
In the ‘Dictionary of Medical Biography,’ published by World Foundation, enlists names of 1100 Medical Scientists from 100 countries around the world for their path breaking contributions to the medical science. Only three names found their place in that dictionary from the city of Kolkata. The names are: Sir Ronald Ross, U.N. Bramhachari and Dr. Mukhopadhyay. What is more ridiculous is that after his death, in 1983, one by one three scientists Howard Jones, Gleicher and Trounson (Australia) in three separate research claimed the invention of Human test tube baby. All these three research were already successfully accomplished by Mukhopadhyay long before their time. One of these scientists even found his research published in the famous Journal “Nature”.
Kolkata
Kolkata , formerly known as Calcutta, is the capital of the Indian state of West Bengal. Located on the east bank of the Hooghly River, it was the commercial capital of East India...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
.
Early life
He was born on January 16, 1931 in Hazaribag, Bihar (now in jharkhand), India. He studied and graduated (in 1955) with an honours degree in physiology from the Calcutta National Medical CollegeCalcutta National Medical College
Out of the six medical colleges in Kolkata , Calcutta National Medical College has its origin in the then founded National Medical Institute or "Jatiya Ayurbigyan Vidyalaya" on 1st of Baisakh in 1921. This institute is a product of the historical Non-cooperation movement. It was inaugurated by...
, which was then affiliated with the prestigious University of Calcutta
University of Calcutta
The University of Calcutta is a public university located in the city of Kolkata , India, founded on 24 January 1857...
. He would later earn a doctorate from the University of Calcutta in 1958 reproductive physiology under the stewardship of Prof. Sachchidananda Banerjee. Later he would earn a second doctorate from the University of Edinburgh
University of Edinburgh
The University of Edinburgh, founded in 1583, is a public research university located in Edinburgh, the capital of Scotland, and a UNESCO World Heritage Site. The university is deeply embedded in the fabric of the city, with many of the buildings in the historic Old Town belonging to the university...
in 1967 in reproductive endocrinology,
His life and death has been the subject of countless newspaper reviews and inspired the Hindi
Hindi
Standard Hindi, or more precisely Modern Standard Hindi, also known as Manak Hindi , High Hindi, Nagari Hindi, and Literary Hindi, is a standardized and sanskritized register of the Hindustani language derived from the Khariboli dialect of Delhi...
movie Ek Doctor Ki Maut
Ek Doctor Ki Maut
Ek Doctor Ki Maut is a 1990 award winning film by noted Bengali director Tapan Sinha, which depicts the ostracism, bureaucratic negligence, reprimand and insult of a doctor and his research, instead of recognition...
(Death of a doctor), directed by Tapan Sinha
Tapan Sinha
Tapan Sinha , was a Indian film director. He was arguably the most uncompromising filmmaker outside the orbit of Parallel Cinema.-Personal life and background:...
.
Career
He created history when he became the first physician in India (and second in the world after BritishUnited Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
physicians Patrick Steptoe
Patrick Steptoe
Patrick Christopher Steptoe FRS was a British obstetrician and gynaecologist and a pioneer of fertility treatment. Steptoe was responsible with biologist and physiologist Robert Edwards for developing in vitro fertilization...
and Robert Edwards) to perform the In vitro fertilization resulting in a test tube baby "Durga" (alias Kanupriya Agarwal) on October 3, 1978.
Facing social ostracization, bureaucratic negligence, reprimand and insult
Insult
An insult is an expression, statement which is considered degrading and offensive. Insults may be intentional or accidental...
instead of recognition
Recognition (sociology)
Recognition in sociology is public acknowledgement of person's status or merits .When some person is recognized, he or she is accorded some special status, such as a name, title, or classification...
from the West Bengal government and refusal of the Government of India
Government of India
The Government of India, officially known as the Union Government, and also known as the Central Government, was established by the Constitution of India, and is the governing authority of the union of 28 states and seven union territories, collectively called the Republic of India...
to allow him to attend international conferences, he committed suicide in his Calcutta residence on 19 June 1981.
His feat has been given belated recognition as the Indian physician who in 1986 was "officially" regarded as being the first doctor to perform in-vitro fertilization in India.
His recognition is attributable to TC Anand Kumar who is credited to be the mastermind behind India's second (officially the first) test-tube baby. Kumar took the crown off his own head after reviewing Subhash Mukhopadhyay's personal notes. He was ably helped by Sunit Mukherji, who was a one-time colleague of Mukhopadhyay.
Kumar is currently active in setting up a research institute in reproductive biology
Reproductive biology
Reproductive biology is a study mainly involving the reproductive system and sex organs. It is closely related to reproductive endocrinology and infertility. also is miotosis and miosis...
in memory of Mukhopadhyay.
Collection and evaluation of spermatozoa
Durga’s father was found to have a low sperm count, according to Mukherjee who obviously was aware of the diagnostics value of semenograms as evidence by the papers he represented much before the WHO laboratory manual for the examination of human semen came out in 1980.Ovarian stimulation. In his report dated 19-10-1978 to the DHS, Mukherjee stated that he had treated Mrs Agarwal with hMG ampoules given twice a day and on alternate days and starting from day 3 to day 9 of the cycle. She was given 6000 I.U. of hCG on day 11 of the cycle and she was subjected to oocyte aspiration some 48h later. Mukherjee was able to aspirate 5 folicle by this method. In today's context this ovarian protocol will not sound outrageous because controlled ovarian hyperstimulation is the standard procedure for all women subjected to IVF. However, until 1980 December ‘conventional wisdom’ in Britain, Australia and USA dictated that stimulated cycles were unsuitable for oocyte collection and therefore oocyte aspiration was restricted to natural cycles. It was only in 1981 that other scientists resorted to ovarian stimulation. The Australians who were the next to announce the birth of IVF babies, began to use clomiphene citrate for ovarian stimulation in 1981. The Norfolk group in the USA, who were the third to report the occurrence of an IVF baby, began to use hMC and hCG in their IVF programme with success in 1982. It is noteworthy that Mukherjee was far ahead of his time in successfully using an ovarian stimulation protocol before anyone else in the world had thought of doing so.
Ovum pick-up for IVF was a problem during the early days. The British team had used a laparascope to harvest oocytes. The advent of ultrasonography later on opened out a new avenue to aspirate oocytes transvesically under ultrasound guidance by making a percutaneous insertion of a long needle traversing the abdominal wall, the urinary bladder and finally the ovarian follicle. The advent of the transvaginal probe has made it possible to collect oocytes per vaginam and this is the standard procedure used now.
Mukherjee ’s originality was that he was able to access the ovaries by a very simple operation on the wall of the vagina. Stimulated ovaries enlarge and drop down towards the Pouch of Douglas. A small incision on the posterior wall of the vagina would allow the ovaries to fall into this opening. This reminds one of how a biologist gains rapid access to the ovaries of rats by a very simple lateral, abdominal incision. The entire procedure was accomplished within a couple of minutes. Mukherjee ’s research experience with rats and humans had helped him take this very simple and original approach of gaining access to ovaries by posterior colpotomy.
One wonders why this very simple approach did not gain popularity. After all today oocytes are aspirated per vaginam under ultrasound guidance.
In vitro culture techniques
The freshly aspirated oocytes were incubated for 4 hours before inseminating them with the husband’s semen that was processed in protein-supplemented Tyrode's solution. This is exactly what is done even to this day in almost all IVF programmes to accomplish in vitro oocyte maturation; processing semen is essential for ‘sperm activation’. The oocytes were exposed to processed semen for a period of 24 hours and later incubated for another 72 hours in a mixture of cervical-uterine fluids. The use of such fluid is not described elsewhere. However, the use of a synthetic fluid, similar to that found in the human Fallopian tube, has been described to be useful for in vitro embryo culture procedures.The methods of in vitro fertilization and embryo growth are described in detail in Mukherjee ’s letter to the DHS dated 19 October 1978 as well as in a publication in an obscure journal. Mukherjee ’s stated ‘…It also appears that for cryogenic preservation of embryos with a relatively larger number of blastomeres (more than 8 cells) may be preferable’.
‘Few pre-ovulatory human oocytes collected from a married woman by surgery were fertilized with spermatozoa from the husband and cleaved in vitro and subsequently frozen slowly to about 196oC after stepwise treatment with dimethyl sulfoxide. One such frozen embryo was subsequently thawed slowly and when transferred into the uterus of the woman apparently resulted in the production of a clinically normal female baby after normal period of gestation’.
Here is clear published evidence of how exactly Mukherjee carried out his version of in vitro fertilization and embryo transfer.
Cryopreservation of embryos from mice, rabbits, sheep and goats were reported between 1971 and 1979. The first report on the successful cryopreservation of four to eight cell human embryos appeared as late as 1981 and Trounson and Mohr reported the first successful clinical outcome of the transfer of thawed human embryos in 1983. A WHO report states ‘embryo cryopreservation has now become a routine adjunct to IVF procedures, and various methods of freezing are employed. The method that has yielded the best results in terms of simplicity, efficiency and reproducibility is one that involves freezing of one to three-day-old embryos (one to eight cells) in a controlled biological chamber that cools the embryos to sub-zero temperatures in the presence of a cryoprotectant 1,2 propanediol. Other cryoprotectants that are used are dimethyl sulfoxide (the same cryoprotectant was used by Mukherjee ) and glycerol.
It may be noted that Subhas Mukherjee reported the successful cryopreservation of an eight cell embryo, storing it for 53 days, thawing and replacing it into the mother’s womb, resulting in a successful and live birth as early as 1978- a full five years before anyone else had done so. This small publication of Mukherjee in 1978 clearly shows that Mukherjee was on the right line of thinking much before anyone else had demonstrated the successful outcome of a pregnancy following the transfer of a 8-cell frozen-thawed embryo into human subjects transferring 8-cell cryopreserved embryos.” (Current Science, Vol .72. No. 7, 10th april1997)
End of experiment
18 November 1978. An ‘expert committee’ was appointed by the Government of West Bengal under the medical association to decide over the fate of a convict named Dr. Subhas Mukhopahyay. His charges are, one, he claims to be the architect of first human test tube baby named Durga (3 October 1978). Secondly, he announced the report to the media before being cleared by the Government bureaucrats. Thirdly, he made this impossible possible with few general apparatus and a refrigerator in his small southern avenue flat while others cannot even think of it, although, having all the expensive resources in their hand (in this research Mukhopadhyay was assisted by Sunit Mukherji and S.K. Bhattacharya). Fourth and most important allegation, he never let his head down by the Government Bureaucrats and his straightforwardness always attracted jealousy out of his peers. The committee was presided over by a Radio physicist and it was composed of a gynecologist, a psychologist, a physicist and a neurologist. None of them had any knowledge about modern reproductive technology. “Where did you keep these embryos?” Mukhopahdhyay said “in sealed ampules.” Then he asked again “How did you seal an ampule?” Speechless Mukhopadhyay could only utter “pardon?” From here started a questioning and counter questioning session which need not to be mentioned was utterly meaningless. “Oh! Embryos do not die while sealing?” there were people who never saw embryos in the entire span of their lifetime.The Committee put forward its final verdict, “Everything that Dr. Mukhopadhyay claims is bogus.”
Only 67 days earlier, on 25 July 1978, world’s first human test tube baby Louise Joy Brown was born at Oldham General Hospital in England. Architects were Robert Edward and Patrick Steptoe. In their procedure they collected an ovum by using a laparoscope. At first they observed the evolution and development of the ovum for a long time and then collected it through a small incision. The ovum thus collected is then fertilized by sperm on a small disc. When it forms into an embryo scientists placed it into the womb. But Mukhopadhyay without using a laparoscope collected the ovum by performing a small operation in the vagina. He increased the number of ova collected by using hormones and developed an embryo. Lastly, he placed it in the womb.
Thanks to his peers and Government bureaucrats he was ultimately handed a punishment. He had been transferred to an ophthalmic department which sealed his prospect of working on hormones.
Late recognition
An insulting silence carried on with every passing day. According to Scientific records, “Harsha” (born 16 August 1986) become the first human test tube baby of India. The credit for this achievement went to T.C Anand Kumar, Director of IRR (ICMR). In 1997, he went to Kolkata to participate in a Science Congress. It was there that all the research documents of Mukhopadhyay were handed over to him. After meticulously scrutinising and having discussions with Durga’s parents, he became certain that Mukhopadhyay was the architect of first human test tube baby in India. This eminent scientist once mentioned in a journal on ‘A critique of Mukherjee ’s technique’:“The brief description given by Mukherjee in his letter dated 19 October 1978 to the Director of Health Services, Government of West Bengal, the reports he gave over the television interviews and reported in the lay press describe how Mukherjee carried out the procedure of in vitro fertilization.
In T.C. Anand Kumar’s initiative, Mukhopahdhyay was mentioned as the architect of first Indian test tube baby in a document related to the subject of artificial intercourse in ICMR. India’s first test tube baby “Durga”, whose parental name is Kanupriya Agarwal, works in a Multinational Company as a Marketing Executive in Delhi. On her 25th birthday she first exposed her identity in a ceremony organized in the memory of Mukhopahdhyay. She spoke about her creator in front of the media and proved once again that her creator’s claim was not bogus.
In the ‘Dictionary of Medical Biography,’ published by World Foundation, enlists names of 1100 Medical Scientists from 100 countries around the world for their path breaking contributions to the medical science. Only three names found their place in that dictionary from the city of Kolkata. The names are: Sir Ronald Ross, U.N. Bramhachari and Dr. Mukhopadhyay. What is more ridiculous is that after his death, in 1983, one by one three scientists Howard Jones, Gleicher and Trounson (Australia) in three separate research claimed the invention of Human test tube baby. All these three research were already successfully accomplished by Mukhopadhyay long before their time. One of these scientists even found his research published in the famous Journal “Nature”.
External links
- http://drsubhasmukhopadhyay.blogspot.com/
- Late honour for test tube pioneer
- It's official: Kanupriya's India’s first test-tube girl
- Indian lost test tube baby race to Edwards by 67 days - TNN